Basic Study Design

This randomized, controlled trial studied the feasibility and safety of long-term, moderate calorie restriction. It also examined its effects on predictors for longevity.

To date, this is the largest study to examine the effects of long-term calorie restriction in adults. Non-obese men and women, aged 21–51 years, participated in the study for 2 years.

The participants were randomly assigned to one of two groups:

Calorie restriction: Participants in this group cut their daily calorie intake by 25%, designed to cause a 15.5% weight loss over 2 years.

Control: In this group, the participants changed none of their dietary habits.

At regular intervals during the study, the researchers measured several factors, including the change in resting metabolic rate, blood levels of triiodothyronine (T3) and tumor necrosis factor-α (TNF-α).

A total of 188 people completed the study, or 86% of those who started.

Bottom Line: This was a randomized, controlled trial examining the effects of sustained calorie restriction on predictors of longevity.

Finding 1. Calorie Restriction Slowed Metabolism

Metabolic rate is a measure of metabolism that estimates the amount of calories used by the body at a given time. In animals, a low resting metabolic rate (RMR) has been associated with increased life span (8, 9).

In the present study, resting metabolic rate decreased significantly more in those who were on a reduced-calorie diet.

This difference in RMR across groups was mostly explained by the greater weight loss among those who were on a reduced-calorie diet.

However, starvation response was also responsible for some of it. Starvation response was estimated as the difference between measured and predicted RMR.

In the first year of the study, the participants lost 10% of their initial body weight, on average. But because of metabolic slowdown, body weight stabilized in the second year of the study.

Bottom Line: Sustained calorie reduction led to slower metabolism or a decreased resting metabolic rate (RMR). This was caused by weight loss as well as the starvation response.

Finding 2. Calorie Restriction Reduced Triiodothyronine (T3)

Triiodothyronine (T3) is a thyroid hormone that affects metabolism, body temperature and heart rate. Low thyroid activity has been associated with longevity in animals (10).

The present study showed that T3 decreased by more than 20% in those who were on a reduced-calorie diet, as shown in the chart below.

Bottom Line: Levels of the thyroid hormone triiodothyronine (T3) decreased significantly on the reduced-calorie diet. Reduced T3 has been associated with longevity in animal studies.

Finding 3. Calorie Restriction Lowered TNF-α

Tumor necrosis factor alpha (TNF-α) is an inflammatory marker. High levels of TNF-α indicate systemic inflammation, and in animal studies, low levels of TNF-α have been associated with longevity (11).

In the present study, levels of TNF-α decreased significantly in those who were on a reduced-calorie diet, as shown in the chart below.

These findings are consistent with observational studies showing lower TNF-α in people who have been on a reduced-calorie diet for a long time (12).

Potential Adverse Events

For most of the participants, moderately reducing calories did not appear to have any serious adverse effects. However, a few of the participants were withdrawn from the study due to health problems.

These included a decrease in bone mineral density, and anemia that didn’t improve with treatment. Additionally, one participant lost too much weight.

Overall, bone mineral density was significantly reduced in the calorie-restricted group, compared to the control group. However, these decreases were small.

This suggests that sustained calorie restriction may, over many years or decades, lead to osteoporosis and fractures.

However, it is unclear whether this is caused by calorie restriction itself or an insufficient intake of certain nutrients.

Bottom Line: Moderate calorie restriction is generally safe for most healthy people, as long as the intake of essential nutrients is sufficient. However, this may depend on the individual.

Limitations

This study appears to have been designed and implemented well, with no apparent limitations.

During the study, however, the calorie-restricted group only lost 10% of their initial body weight, not the expected 15.5%.

This is because the participants did not achieve the planned 25% calorie restriction, but only about 12%. Why this happened is unclear, but it might have been due to lack of compliance and/or an inaccurate study design.

Also, the study’s findings are limited to highly motivated, healthy, non-obese individuals. Sustained calorie restriction may have different effects in other groups.

Bottom Line: The study was planned and implemented well. However, participants did not achieve the planned 25% calorie restriction.

Summary and Real-Life Application

In short, the study showed that moderate, long-term calorie restriction is both feasible and safe for healthy, non-obese people.

Although the effects on life span couldn’t be measured directly, a reduced-calorie diet improved several health aspects related to longevity.

Simply put, moderately reducing calories may have many potential benefits, as long as the intake of essential nutrients is adequate.

In some cases, however, reducing calories can be downright harmful. If you are not overweight, consult with your doctor before going on a reduced-calorie diet.